TABLE 3

Support and confounds for proposed DOPr trafficking pathways

Controversy: Regulated (Secretory) vs Constitutive Trafficking: Does Secretory Pathway Exist?
SecretoryConstitutive
Support:
  • Colocalization with substance P in large dense core vesicles  (light and electron microscopy)

  • Ephys supports co-localization of CGRP and DOPr

  • PPTA KO shows decreased DOPr in plasma membrane

  • PPTA KO shows decreased DOPr radioligand binding

  • Enhanced DOPr agonist analgesia is absent in PPTA KO mice

Support:
  • All literature agree in constitutive trafficking of DOPr

  • Evidence that it involves cytoskeletal proteins including  cofilin and beta-arrestin-1

Confounds:
  • DOPr antibody labeling is decreased in PPTA KO mice (may show cross reactivity with SP)

  • SP and DOPr co-localization are not present in DRG of DOPr-GFP mice, but is present in myenteric plexus

  • In situ studies show both co-localization of SP and DOPr and no co-localization

  • GFP visualization in secretory pathways is confounded by oligomerization.

  • Tissue isolation (itself) for ex vivo and in vitro studies may trigger DOPr trafficking

Confounds:
  • None (to our knowledge)